{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:10:42Z","timestamp":1760854242932,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["NN125601"],"award-info":[{"award-number":["NN125601"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: Absence seizures (ASs) are sudden, transient lapses of consciousness associated with lack of voluntary movements and generalized 2.5\u20134 Hz spike-wave discharges (SWDs) in the EEG. In addition to the thalamocortical system, where these pathological oscillations are generated, multiple neuronal circuits have been involved in their modulation and associated comorbidities including the serotonergic system. Neuronal activity in one of the major synaptic input structures to the brainstem dorsal raph\u00e9 nucleus (DRN), the lateral hypothalamus (LH), has not been characterized. (2) Methods: We used viral tract tracing and optogenetics combined with in vitro and in vivo electrophysiology to assess the involvement of the LH in absence epilepsy in a genetic rodent model. (3) Results: We found that a substantial fraction of LH neurons project to the DRN of which a minority is GABAergic. The LH to DRN projection can lead to monosynaptic iGluR mediated excitation in DRN 5-HT neurons. Neuronal activity in the LH is coupled to SWDs. (4) Conclusions: Our results indicate that a brain area involved in the regulation of autonomic functions and heavily innervating the RN is involved in ASs. The decreased activity of LH neurons during SWDs could lead to both a decreased excitation and disinhibition in the DRN. These results support a long-range subcortical regulation of serotonergic neuromodulation during ASs and further our understanding of the state-dependence of these seizures and some of their associated comorbidities.<\/jats:p>","DOI":"10.3390\/ijms22179466","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T08:42:32Z","timestamp":1630399352000},"page":"9466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures"],"prefix":"10.3390","volume":"22","author":[{"given":"P\u00e9ter","family":"Sere","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged, 6726 Szeged, Hungary"},{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolett","family":"Zsigri","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged, 6726 Szeged, Hungary"},{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timea","family":"Raffai","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged, 6726 Szeged, Hungary"},{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szabina","family":"Furdan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged, 6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanni","family":"Gy\u0151ri","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged, 6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Crunelli","sequence":"additional","affiliation":[{"name":"Neuroscience Division, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magor L.","family":"L\u0151rincz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged, 6726 Szeged, Hungary"},{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"},{"name":"Neuroscience Division, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1093\/brain\/awaa072","article-title":"Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures","volume":"143","author":"Crunelli","year":"2020","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1212\/WNL.0000000000003480","article-title":"Second monotherapy in childhood absence epilepsy","volume":"88","author":"Cnaan","year":"2017","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/epi.12028","article-title":"Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: Initial monotherapy outcomes at 12 months","volume":"54","author":"Glauser","year":"2013","journal-title":"Epilepsia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1212\/WNL.0b013e3182a9f3ca","article-title":"Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy","volume":"81","author":"Masur","year":"2013","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/j.1471-4159.2006.04277.x","article-title":"Serotonin and epilepsy","volume":"100","author":"Bagdy","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2004.01.072","article-title":"Selective 5-HT1A and 5-HT7 antagonists decrease epileptic activity in the WAG\/Rij rat model of absence epilepsy","volume":"359","author":"Graf","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1254\/jphs.10156FP","article-title":"Serotonergic modulation of absence-like seizures in groggy rats: A novel rat model of absence epilepsy","volume":"114","author":"Ohno","year":"2010","journal-title":"J. Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1684\/j.1950-6945.2002.tb00547.x","article-title":"The control of seizures by the basal ganglia? A review of experimental data","volume":"4","author":"Deransart","year":"2002","journal-title":"Epileptic Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0014-2999(93)90962-H","article-title":"Effects of cholinergic drugs on genetic absence seizures in rats","volume":"234","author":"Danober","year":"1993","journal-title":"Eur. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/0014-2999(87)90690-X","article-title":"Effects of drugs affecting noradrenergic neurotransmission in rats with spontaneous petit mal-like seizures","volume":"135","author":"Micheletti","year":"1987","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.brainresbull.2004.11.004","article-title":"Reduction of adrenergic neurotransmission with clonidine aggravates spike-wave seizures and alters activity in the cortex and the thalamus in WAG\/Rij rats","volume":"64","author":"Sitnikova","year":"2005","journal-title":"Brain Res. Bull."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev-clinpsy-032210-104533","article-title":"Treatment of obsessive compulsive disorder","volume":"7","author":"Franklin","year":"2011","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/nrd1821","article-title":"Case history: The discovery of fluoxetine hydrochloride (Prozac)","volume":"4","author":"Wong","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/35072566","article-title":"Research and treatment approaches to depression","volume":"2","author":"Wong","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1523\/JNEUROSCI.4331-15.2016","article-title":"Impaired serotonergic brainstem function during and after seizures","volume":"36","author":"Zhan","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.physbeh.2006.09.020","article-title":"Propagation of spike and wave activity to the medial prefrontal cortex and dorsal raphe nucleus of WAG\/Rij rats","volume":"90","author":"Olah","year":"2007","journal-title":"Physiol. Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.neuropharm.2016.04.016","article-title":"Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures","volume":"108","author":"Venzi","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.celrep.2014.06.042","article-title":"Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatory systems","volume":"8","author":"Ogawa","year":"2014","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.neuron.2014.06.024","article-title":"Presynaptic partners of dorsal raphe serotonergic and GABAergic neurons","volume":"83","author":"Weissbourd","year":"2014","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.neuron.2010.11.032","article-title":"Sleep state switching","volume":"68","author":"Saper","year":"2010","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0149-7634(95)00015-1","article-title":"The lateral hypothalamic area revisited: Ingestive behavior","volume":"20","author":"Bernardis","year":"1996","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nn.4209","article-title":"Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness","volume":"19","author":"Herrera","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4840","DOI":"10.1523\/JNEUROSCI.2850-20.2021","article-title":"Reciprocal Lateral Hypothalamic and Raphe GABAergic Projections Promote Wakefulness","volume":"41","author":"Gazea","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/cne.1105","article-title":"Orbitomedial prefrontal cortical projections to hypothalamus in the rat","volume":"432","author":"Floyd","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/cne.20738","article-title":"Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers","volume":"492","author":"Gabbott","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/cne.902900205","article-title":"Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: An anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin","volume":"290","author":"Sesack","year":"1989","journal-title":"J. Comp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/s41593-018-0130-4","article-title":"Cortical drive and thalamic feed-forward inhibition control thalamic output synchrony during absence seizures","volume":"21","author":"McCafferty","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0006-8993(90)91638-W","article-title":"Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized non-convulsive epilepsy","volume":"523","author":"Vergnes","year":"1990","journal-title":"Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/nature07709","article-title":"The subcellular organization of neocortical excitatory connections","volume":"457","author":"Petreanu","year":"2009","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fnana.2014.00086","article-title":"Long-term Cre-mediated retrograde tagging of neurons using a novel recombinant pseudorabies virus","volume":"8","author":"Oyibo","year":"2014","journal-title":"Front. Neuroanat."},{"key":"ref_31","first-page":"37","article-title":"Genetic absence epilepsy in rats from Strasbourg\u2014A review","volume":"35","author":"Marescaux","year":"1992","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/cercor\/bhn237","article-title":"Inactivation of the somatosensory cortex prevents paroxysmal oscillations in cortical and related thalamic neurons in a genetic model of absence epilepsy","volume":"19","author":"Polack","year":"2009","journal-title":"Cereb. Cortex"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mickelsen, L.E., Kolling, F.W., Chimileski, B.R., Fujita, A., Norris, C., Chen, K., Nelson, C.E., and Jackson, A.C. (2017). Neurochemical heterogeneity among lateral hypothalamic hypocretin\/orexin and melanin-concentrating hormone neurons identified through single-cell gene expression analysis. eNeuro, 4.","DOI":"10.1523\/ENEURO.0013-17.2017"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0306-4522(03)00518-9","article-title":"Neurochemical and anatomical identification of fast- and slow-firing neurones in the rat dorsal raphe nucleus using juxtacellular labelling methods in vivo","volume":"122","author":"Allers","year":"2003","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1523\/JNEUROSCI.3008-15.2016","article-title":"Optogenetic activation of dorsal raphe serotonin neurons rapidly inhibits spontaneous but not odor-evoked activity in olfactory cortex","volume":"36","author":"Lottem","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3892\/etm.2021.10341","article-title":"Psychiatric comorbidities in adult patients with epilepsy (A systematic review)","volume":"22","author":"Gurgu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107797","DOI":"10.1016\/j.yebeh.2021.107797","article-title":"Vortioxetine increases absence-like seizures in WAG\/Rij rats but decreases penicillin- and pentylenetetrazole-induced seizures in Wistar rats","volume":"116","author":"Aygun","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nat. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9466\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:53:26Z","timestamp":1760165606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22179466"],"URL":"https:\/\/doi.org\/10.3390\/ijms22179466","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,8,31]]}}}